Colonization resistance: training and research towards microbiome derived solutions to foodborne disease

Informations projet

COL_RES

N° de convention de subvention: 956279

DOI

10.3030/956279

Projet clôturé

Date de signature de la CE 27 Juillet 2020

Date de début 1 Mars 2021

Date de fin 28 Février 2025

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 2 186 997,48

Contribution de l’UE

€ 2 186 997,48

Coordonné par

UNIVERSITY COLLEGE CORK - NATIONAL UNIVERSITY OF IRELAND, CORK
Ireland

Periodic Reporting for period 2 - COL_RES (Colonization resistance: training and research towards microbiome derived solutions to foodborne disease)

Période du rapport: 2023-03-01 au 2025-02-28

Résumé du contexte et des objectifs généraux du projet

The gut microbiota provides a significant barrier to foodborne infection through a mechanism called colonization resistance. However relatively little is known about particular bacterial species in the GI tract that contribute to colonization resistance or the mechanisms by which the exclusion of particular pathogens occurs. Understanding colonization resistance and identifying the key bacterial species involved will inform the design of rational probiotic and pharmaceutical strategies to prevent or treat foodborne infection.
Every year there are an estimated 600 million cases of foodborne infection globally with 420,000 deaths. In the WHO European Region approximately 23 million people fall ill annually from foodborne infection with an estimated 4654 deaths. The impacts for society both globally and locally within the European Region, are clearly highly significant.
The overall objectives of COL_RES are to examine the mechanisms by which the gut microbiota protects against serious foodborne pathogens (Salmonella, E. coli, Listeria, Citrobacter rodentium and Campylobacter) in order to identify potential probiotics that can protect against individual or multiple infectious agents. The network employed a systems biology-based approach by exploiting a variety of research models at world-leading laboratories, combined with metabolomics, bioinformatics and phage therapeutics to generate multi-omics data that has uncovered mechanisms by which the gut microbiota protects against specific foodborne pathogens and has informed the development of model experimental systems. Throughout the collaborative research programme COL_RES provided state-of-the-art training for 8 early-stage researchers preparing them for problem solving and entrepreneurial roles in industry and society and underpinning cutting-edge research in infectious disease in the EU. All 8 ESRs have completed (or are due to complete) their PhD studies.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Eight ESRs were recruited and registered for their PhDs in their host institutions (University College Cork, Ireland; ETH-Zürich; Imperial College London; Universite Clermont Auvergne; Charite University, Berlin; Eurecat, Tarragona). Training was aligned to the personal career goals of the ESRs and subjects included: bioinformatics, data analysis, intellectual property/entrepreneurship. ESRs presented at large international conferences (including the FEMS Congress in Hamburg, the International Gut Microbiology Symposium in Aberdeen and a COL_RES/University of Galway-hosted Irish Pathogen Biology Conference). All ESRs completed secondments that were appropriate to their research projects and training needs including intersectoral secondments to SeqBiome and training secondments between the partner research institutions (including Yale University). ESRs interacted regularly through secondments as well as during COL_RES organised events in Tarragona, Hamburg and Galway, online meeting updates and workshops and a site visit to the COL_RES industry partner Pintaluba, Spain. ESRs were very active in communicating to the public through Education & Public Engagement (EPE) events which included collectively running a microbiome exhibit at the Cork Carnival of Science (a large 2-day science fair attended by 27,000 visitors), a successful exhibit at the Science is Wonderful fair in Brussels (over 5,000 visitors) and multiple other EPE events including European Researchers Night, FAMELAB, Pint of Science and Native Scientist.
COL_RES ESRs have published 15 papers at the time of writing with numerous other manuscripts submitted or in-preparation. A collaboration based upon multiple secondments to ETH-Zürich has established a defined microbiota OligoMM12 mouse model as a significant model system for analysing our pathogens (published in Gut Microbes). The COL_RES programme provided further insights into the mechanisms that underpin colonization resistance against Campylobacter as well as Salmonella, Listeria and Enterohaemorrhagic E. coli (EHEC) infection (incl. papers in Nat. Commun, Frontiers in Microbiology, Eur. Journal of Microbiol & Immunol and Microbial Cell). The research has identified a number of potential probiotic strains that show promise in the inhibition of Salmonella, Campylobacter and Listeria. The work has also isolated novel bacteriophage (bacterial viruses) as potential therapeutics against both Listeria monocytogenes and Citrobacter. Other research breakthroughs have been made in the development of new computational tools for analysis of genetic and chemical (metabolite) data which will be of use to the international research community (incl. a paper in Analytical Chem).

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Research work has progressed beyond the state-of-the-art. A large-scale collaborative study in COL_RES was the first to investigate the defined microbiota murine model system, OligoMM12 mice, against a range of different foodborne agents in a single controlled study (Gut Microbes (2025)). The work demonstrated that this is an excellent model for studying Campylobacter infections as it recapitulated many facets of human disease. Further insights demonstrated the significant role of secondary bile acids and nutritional factors in limiting Campylobacter infection and pinpointed specific probiotic strains as potential therapeutics (published in Frontiers in Microbiology (2023) and the European Journal of Microbiology & Immunology (2025)). Similarly, an extension of our work in OligoMM12 mice showed that specific probiotic strains displayed efficacy against Salmonella infection (manuscript in preparation). In another study outgrowth of both commensal E. coli and Salmonella could be seen in a sepsis OligoMM12 mouse model, demonstrating how systemic inflammation can enhance microbial pathogenesis in the gut (published in Nature Communications, 2025).
The use of the above models allowed investigation of the impact of complex inflammatory processes on pathogenesis in the context of diet and sepsis. However, we also developed animal-free models of the human gut microbiota and provided insights into diet-associated and age-related changes to the microbiota which impact proliferation of EHEC (published in Nutrients (2024) and Microbial Cell (2025)) as well as Listeria (manuscripts in preparation) in such models.
Given the scientific (and societal) importance of big data analysis, our ESRs all received significant training in bioinformatics and data integration. This was facilitated through collaborative activities within the programme involving experts in bioinformatics and chemical analytics (metabolomics). ESRs working specifically in these fields have developed improved computational and analytical tools for chemical (metabolite) analysis (paper published in Analytical Chemistry (2024)), identification of bacterial species from genetic data (manuscript in preparation) and methods to analyse multicomponent datasets (paper in preparation).
Overall, the COL_RES programme has trained 8 PhD students to a high level through a cutting-edge research and training programme. Importantly we have identified potential probiotic and phage-mediated interactions which have the future potential to impact the significant human cost of foodborne disease (600 million infections per annum globally) to improve quality of life and decrease mortality from foodborne disease.

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